The present invention relates to an angiotensin converting enzyme inhibitor comprising a composition containing peptide obtained by digesting fish meat with thermolysin enzyme, which can be useful for medical supplies, foods, health foods, specified foods for health care and the like.
Angiotensin converting enzyme is an enzyme which is chiefly present in the lung, vascular endothelial cells and renal proximal tubules and acts on angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu (SEQ. ID. NO. 1)) to cleave a dipeptide (His9-Leu10) off its C-terminus to give rise to angiotensin II which has potent pressor activity. Futhermore, this enzyme decomposes bradykinin, a physiological hypotensive substance, to inactivate it and, as such, is intimately involved in the pressor system. It has been considered that inhibition of angiotensin converting enzyme would lower the blood pressure and is, therefore, clinically useful for the prevention and treatment of hypertension.
Recently, since captopril, a proline derivative, was synthesized and found to have hypotensive activity, much research has been undertaken for synthesizing a variety of angiotensin converting enzyme inhibitors and it has also been attempted to isolate such substances from natural resources.
This is because natural type angiotensin converting enzyme inhibitors available from foods or food materials may be expected to be of value as antihypertensive agents of low toxicity and high safety.
The present inventor has already disclosed a novel peptide which contains Leu-Lys-Pro backbone in Japanese Unexamined Patent Application Publication No. 69397/1992. In Japanese Unexamined Patent Application Publication No. 144696/1992, there is disclosed the method of producing a composition having an angiotensin converting enzyme inhibitor which is obtained by hydrolyzing a protein with a thermolysin. Furthermore, in Japanese Unexamined Patent Application Publication No. 244979/1993, there is disclosed a method of producing a composition having an angiotensin converting enzyme inhibitors which is obtained by hydrolyzing the residue mainly comprising water-insoluble protein with a protease after heat-treating meat in water of not less than 50° C. to exclude water-soluble protein by extraction.
However, though an inhibiting activity of novel peptides disclosed in the above-mentioned Japanese Unexamined Patent Publication No. 69397/1992 is very strong, it takes much effort and higher cost to separate the peptide in practice. Also, though a composition having relatively high inhibitory activity is obtained by those methods disclosed in Japanese Unexamined Patent Application Publication No. 144696/1992 and Japanese Unexamined Patent Application Publication No. 244979/1993, a taken amount of the composition is slightly increased in order to obtain effect. Therefore, it is desired that a taken amount be further reduced in order to take the composition readily every day. Furthermore, if dried bonito is used as protein, the above compositions are still open to improvements in an aftertaste though peptide-specific bitterness is reduced.